Accelerated Brain Aging in Adults with Major Depressive Disorder Predicts Poorer Outcome with Sertraline: Findings from the EMBARC Study

Published:September 27, 2022DOI:



      Major depressive disorder (MDD) may be associated with accelerated brain aging (higher brain age than chronological age). This report evaluated whether brain age is a clinically useful biomarker by checking its test-retest reliability using magnetic resonance imaging (MRI) scans acquired one week apart and by evaluating the association of accelerated brain aging with symptom severity and antidepressant treatment outcomes.


      Brain age was estimated in participants of Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study using T1-weighted structural MRI [MDD N=290; female N=192; healthy control (HC) N=39; female N=24]. Intraclass correlation coefficient (ICC) were used for baseline-to-week-1 test-retest reliability. Association of baseline Δ brain age (brain age minus chronological age) with Hamilton Depression Rating Scale (HAMD-17) and Concise Health Risk Tracking Self-Report (CHRT-SR) domains [impulsivity, suicide propensity (measures pessimism, helplessness, perceived lack of social support, and despair), and suicidal thoughts] were assessed at baseline (linear regression) and during 8-week-long treatment with either sertraline or placebo (repeated-measures mixed models).


      Mean (±standard deviation) baseline chronological age, brain age, and Δ brain age were 37.1±13.3, 40.6±13.1, and 3.1±6.1 years in MDD and 37.1±14.7, 38.4±12.9, and 0.6±5.5 years in HC groups, respectively. Test-retest reliability was high (ICC=0.98-1.00). Higher baseline Δ brain age in MDD group was associated with higher baseline impulsivity and suicide propensity, and predicted smaller baseline-to-week-8 reductions in HAMD-17, impulsivity, and suicide propensity with sertraline but not with placebo.


      Brain age is a reliable and potentially clinically useful biomarker that can prognosticate antidepressant treatment outcomes.


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